Effect of the local energy distribution of x-ray beams generated through inverse Compton scattering in dual-energy imaging applications.

X-ray sources based on the inverse Compton interaction between a laser and a relativistic electron beam are emerging as a promising compact alternative to synchrotron for the production of intense monochromatic and tunable radiation. The emission characteristics enable several innovative imaging techniques, including dual-energy K-edge subtraction (KES) imaging. The performance of these techniques is optimal in the case of perfectly monochromatic x-ray beams, and the implementation of KES was proven to be very effective with synchrotron radiation. Nonetheless, the features of inverse Compton scattering (ICS) sources make them good candidates for a more compact implementation of KES techniques. The energy and intensity distribution of the emitted radiation is related to the emission direction, which means different beam qualities in different spatial positions. In fact, as the polar angle increases, the average energy decreases, while the local energy bandwidth increases and the emission intensity decreases. The scope of this work is to describe the impact of the local energy distribution variations on KES imaging performance. By means of analytical simulations, the reconstructed signal, signal-to-noise ratio, and background contamination were evaluated as a function of the position of each detector pixel. The results show that KES imaging is possible with ICS x-ray beams, even if the image quality slightly degrades at the detector borders for a fixed collimation angle and, in general, as the beam divergence increases. Finally, an approach for the optimization of specific imaging tasks is proposed by considering the characteristics of a given source.

ACACIAS 1: The physiological and subjective impacts of high fidelity simulation of the breaking of bad news.

STUDY OBJECTIVE: Breaking bad news (BN) is difficult and necessitates targeted training. To be effective, training may call for High Fidelity Simulation (HFS). This prospective study was conducted to objectively assess the impact of HFS as a tool conducive to the development of clinical competence in situations involving the delivery of bad news. METHODS: This feasibility study was conducted from January to May 2021 and included students in medical oncology and digestive surgery. The subjective and objective impacts of HFS were evaluated by means of a self-administered questionnaire and a wristband, Affect-tag, which recorded several indicators: emotional power (EP), emotional density (DE) and cognitive load (CL) in students undergoing training. RESULTS: Forty-six (46) students with a median age of 25 years (21-34 years) were included. While the participants were effectively and emotionally involved in the HFS training, they were not completely overwhelmed by their emotions, a possible occurrence in this type of program. After two training programs, the students presented with lower EP (P<0.001) and higher DE (P=0.005), while their CL remained stable (P=0.751). The information given in the self-administered questionnaires and the evaluations by outside professionals (actor, nurse, psychologist…) highlighted improved skills. CONCLUSION: Taking into account the emotional parameters observed and the questionnaires collected, HFS can be considered as a suitable and effective tool in the breaking of bad news.

Does increased patient comprehension decrease preoperative anxiety before digestive surgery?

BACKGROUND: There exists a misalignment between the information given by a surgeon and the information retained by the patient. Inability to assimilate relevant information can be a factor of preoperative anxiety. The aim of this study was to assess patients' information retention according to a Fédération de Chirurgie Viscérale et Digestive (FCVD) questionnaire. MATERIALS: From 29 June 2020 to 2 August 2020, a prospective, comparative multicenter study was conducted among 89 patients who were about to undergo digestive surgery. They were included either in a standard group (management in accordance with the usual French guidelines) or experimental group, which received a second consultation, one week before surgery. The day before being operated, all the patients filled out 3 questionnaires analyzing their percentage of retention according to two scales: the Amsterdam Preoperative Anxiety and information Scale (APAIS) and the visual analogue scale for anxiety (VAS-A). RESULTS: Patient comprehension of the FCVD information was 94% and 63% in the experimental and the control groups, respectively (P<0.001). The standard group was significantly more anxious than the experimental group, with VAS-A rates of 6.2 and 4.6 (P=0.014), respectively. On the other hand, according to the APAIS scale, they were similarly anxious, with scores of 11.3 versus 11.9, respectively (P=0.200). CONCLUSION: A second transmission of exhaustive information shortly before digestive surgery was conducive to improved retention. Enhanced comprehension and memorization reduced preoperative anxiety.

Evaluation of microcalcification contrast in clinical images for digital mammography and synthetic mammography.

PURPOSE: The aim of this work was to compare, in a clinical study, digital mammography and synthetic mammography imaging by evaluating the contrast in microcalcifications of different sizes. METHODS: A retrospective review of microcalcifications from 46 patients was undertaken. A Hologic 3-Dimensions mammography system and a HD Combo protocol was used for simultaneous acquisition of the digital and synthetic images. Microcalcifications were classified in accordance with their size, and patient breast images were classified in accordance with their density as adipose, moderately dense and dense. The contrast of the microcalcifications was measured and the contrast ratio between synthetic and digital images was compared. An additional qualitative assessment of the images was presented to correlate the conspicuity of the microcalcifications with the suppression of the structure noise. RESULTS: Microcalcifications in adipose background always exhibit a comparable or better contrast on synthetic images, regardless their size. For moderately dense background, synthetic images show a better contrast in 91.2 % of cases for small microcalcifications and in 90.9 % of cases for large microcalcifications. For a dense background, better contrast is seen in 89.5 % of cases for small microcalcifications, and in 85.7 % of cases for large microcalcifications. The contrast ratio increases with increasing breast glandularity. The suppression of structure noise also contributes to the enhancement of microcalcifications in the synthetic images. CONCLUSIONS: Synthetic mammography imaging is superior to digital mammography imaging in terms of microcalcification contrast, regardless their size and breast density.

10 ns PEFs induce a histological response linked to cell death and cytotoxic T-lymphocytes in an immunocompetent mouse model of peritoneal metastasis.

PURPOSE: The application of nanosecond pulsed electric fields (nsPEFs) could be an effective therapeutic strategy for peritoneal metastasis (PM) from colorectal cancer (CRC). The aim of this study was to evaluate in vitro the sensitivity of CT-26 CRC cells to nsPEFs in combination with chemotherapeutic agents, and to observe the subsequent in vivo histologic response. METHODS: In vitro cellular assays were performed to assess the effects of exposure to 1, 10, 100, 500 and 1000 10 ns pulses in a cuvette or bi-electrode system at 10 and 200 Hz. nsPEF treatment was applied alone or in combination with oxaliplatin and mitomycin. Cell death was detected by flow cytometry, and permeabilization and intracellular calcium levels by fluorescent confocal microscopy after treatment. A mouse model of PM was used to investigate the effects of in vivo exposure to pulses delivered using a bi-electrode system; morphological changes in mitochondria were assessed by electron microscopy. Fibrosis was measured by multiphoton microscopy, while the histological response (HR; hematoxylin-eosin-safran stain), proliferation (KI67, DAPI), and expression of immunological factors (CD3, CD4, CD8) were evaluated by classic histology. RESULTS: 10 ns PEFs exerted a dose-dependent effect on CT-26 cells in vitro and in vivo, by inducing cell death and altering mitochondrial morphology after plasma membrane permeabilization. In vivo results indicated a specific CD8+ T cell immune response, together with a strong HR according to the Peritoneal Regression Grading Score (PRGS). CONCLUSIONS: The effects of nsPEFs on CT-26 were confirmed in a mouse model of CRC with PM.

BriXS, a new X-ray inverse Compton source for medical applications.

MariX is a research infrastructure conceived for multi-disciplinary studies, based on a cutting-edge system of combined electron accelerators at the forefront of the world-wide scenario of X-ray sources. The generation of X-rays over a large photon energy range will be enabled by two unique X-ray sources: a Free Electron Laser and an inverse Compton source, called BriXS (Bright compact X-ray Source). The X-ray beam provided by BriXS is expected to have an average energy tunable in the range 20-180 keV and intensities between 1011 and 1013 photon/s within a relative bandwidth ΔE/E=1-10%. These characteristics, together with a very small source size (~20 µm) and a good transverse coherence, will enable a wide range of applications in the bio-medical field. An additional unique feature of BriXS will be the possibility to make a quick switch of the X-ray energy between two values for dual-energy and K-edge subtraction imaging. In this paper, the expected characteristics of BriXS will be presented, with a particular focus on the features of interest to its possible medical applications.

Comprehensive data set to include interference effects in Monte Carlo models of x-ray coherent scattering inside biological tissues.

Interference effects are included in the x-ray coherent scattering models used in Monte Carlo codes by modifying each material form factor through a proper interference function, which is obtained directly from the measured scattering pattern. This approach is effective for non-biological materials, but it is impractical for biological tissues, due the wide composition variability they can feature. Instead, a given biological sample can be considered as a proper mixture of four basis materials: fat, water, collagen and calcium hydroxyapatite. The sample form factor can then be obtained through a weighted mean of the form factors of the basis materials, which include interference effects. Here, we fully demonstrate the validity of the proposed segmentation method by applying it to 31 biological tissue samples whose form factors are available in the literature. The segmentation, namely the determination of the optimal weight of the basis components, was carried out through a multiple linear regression or, in some cases, by using a controlled trial and error sequence. The form factors of the basis materials were extracted from previous works and elaborated to include more scattering features. In particular, they were interpolated at a denser grid. Furthermore, the data measured separately in wide angle and small angle regimes, for fat and collagen, were merged. In general, a very good agreement was obtained between the original sample and the calculated mixture, being the mean relative difference of their scattering profiles and their attenuation coefficients ∼10%. The segmentation method is fully supported by our extension to the Geant4 model of x-ray coherent scattering, which was used to compare simulated scatter distributions with known experimental data. The developed Geant4 code and a series of molecular form factors, including those of the basis materials, are freely downloadable from a dedicated web repository.

Update on the Surgical Treatment of Pancreatic Neuroendocrine Tumors.

BACKGROUND AND AIMS: Pancreatic neuroendocrine tumors (PNET) arise from uncontrolled proliferation of neuroendocrine cell and further genetic alterations that may induce hormone secretion such as glucagon/insulin/gastrin/VIP. Their incidence is rapidelly growing, especially because of the frequent incidental diagnosis of small asymptomatic non-functionnal neuroendocrine tumors with the widespread use of cross-sectional imaging. The vast majority of pancreatic neuroendocrine tumors are sporadic but up to 5%-10% of them arise from genetic syndromes, the main one being Multiple Endocrine Neopalsm type 1 (MEN1). Appropriate management of patients with PNET is a complex challenge for surgeons, and require extensive medical collaboration. This review aims to summarize major and recent updates regarding the medico-surgical management of PNETs. MATERIAL AND METHODS: Review of pertinent English language literature. RESULTS: This article provides a concise summary of the clinical presentation, diagnosis, surgical management, alternative treatments and follow up of PNETs. CONCLUSION: PNET are a rare, heterogeneous group of neoplasms with a generally favorable prognosis at least compared to pancreatic adenocarcinoma. Surgical resection is the cornerstone of their management, particularly for localized disease, and should always be discussed in multidisciplinary tumor board.

Inverse Compton radiation: a novel x-ray source for K-edge subtraction angiography?

Coronary angiography is clinically used worldwide to diagnose diseases of coronary arteries. Despite its effectiveness, this technique is quite invasive and it is associated with significant risks due to the arterial catheterisation needed to inject the contrast agent. A valid alternative is using the K-edge subtraction (KES) method, which is based on the subtraction of two images acquired at energies bracketing the K-edge of the contrast element. The enhanced sensitivity of KES allows the intravenous injection of the contrast agent, thus reducing the risks of catheterisation. This technique can be effectively implemented by using intense and quasi-monochromatic x-ray beams. Synchrotron radiation has been proven to work well for this purpose, but its cost and size prevent a widespread clinical application. Inverse Compton sources are among the most promising innovative sources of intense and quasi-monochromatic x-rays. These sources are intrinsically more compact than those based on synchrotron radiation. In this work, the potential application of inverse Compton radiation to KES angiography is investigated. To this purpose, after a short review of the physics behind the inverse Compton process, an analytical framework is described. The proposed model is based on the application of the KES algorithm to calculate the SNR of details inside a suitable mathematical phantom. That allowed us to identify the characteristics of an inverse Compton source required for KES imaging. In particular, it was estimated that a photon fluence of 108 ph mm-2 is necessary to detect signals of clinical interest. Novel sources based on inverse Compton promise to achieve this requirement with an acquisition time of few hundreds of ms. This feature, together with compactness, broad two-dimensional radiation field, absence of harmonic contamination and the ability to deliver high photon fluxes also at high energies, makes this kind of sources promising for KES angiography and other diagnostic applications.

Radioisotopic purity and imaging properties of cyclotron-produced 99mTc using direct 100Mo(p,2n) reaction.

Evaluation of the radioisotopic purity of technetium-99m (99mTc) produced in GBq amounts by proton bombardment of enriched molibdenum-100 (100Mo) metallic targets at low proton energies (i.e. within 15-20 MeV) is conducted. This energy range was chosen since it is easily achievable by many conventional medical cyclotrons already available in the nuclear medicine departments of hospitals. The main motivation for such a study is in the framework of the research activities at the international level that have been conducted over the last few years to develop alternative production routes for the most widespread radioisotope used in medical imaging. The analysis of technetium isotopes and isomeric states (9xTc) present in the pertechnetate saline Na99mTcO4 solutions, obtained after the extraction/purification procedure, reveals radionuclidic purity levels basically in compliance with the limits recently issued by European Pharmacopoeia 9.3 (2018 Sodium pertechnetate (99mTc) injection 4801-3). Moreover, the impact of 9xTc contaminant nuclides on the final image quality is thoroughly evaluated, analyzing the emitted high-energy gamma rays and their influence on the image quality. The spatial resolution of images from cyclotron-produced 99mTc acquired with a mini-gamma camera was determined and compared with that obtained using technetium-99m solutions eluted from standard 99Mo/99mTc generators. The effect of the increased image background contribution due to Compton-scattered higher-energy gamma rays (E γ > 200 keV), which could cause image-contrast deterioration, was also studied. It is concluded that, due to the high radionuclidic purity of cyclotron-produced 99mTc using 100Mo(p,2n)99mTc reaction at a proton beam energy in the range 15.7-19.4 MeV, the resulting image properties are well comparable with those from the generator-eluted 99mTc.

Geant4 implementation of inter-atomic interference effect in small-angle coherent X-ray scattering for materials of medical interest.

An extension to Geant4 Monte Carlo code was developed to take into account inter-atomic (molecular) interference effects in X-ray coherent scattering. Based on our previous works, the developed code introduces a set of form factors including interference effects for a selected variety of amorphous materials useful for medical applications, namely various tissues and plastics used to build phantoms. The code is easily upgradable in order to include new materials and offers the possibility to model a generic tissue as a combination of a set of four basic components. A dedicated Geant4 application for the simulation of X-ray diffraction experiments was created to validate the proposed upgrade of Rayleigh scattering model. A preliminary validation of the code obtained through a comparison with EGS4 and an experiment is presented, showing a satisfactory agreement.

Colonic Bacteroides are positively associated with trabecular bone structure and programmed by maternal vitamin D in male but not female offspring in an obesogenic environment.

BACKGROUND/OBJECTIVES: The gut microbiota is determined early in life, possibly including pregnancy. Pioneering data suggest vitamin D, a nutrient important for bone health, affects this microbiota. We found that high maternal vitamin D lowered circulating lipopolysaccharide (LPS), improved intestinal barrier and bone health in male but not female offspring in an obesogenic environment. This study determined if high maternal dietary vitamin D programs Bacteroides and Prevotella and whether this associates with bone mineral content, density and structure of male and female adult offspring fed an obesogenic diet. METHODS: C57BL/6J females received an AIN93G diet with high or low vitamin D from before mating until weaning. Post-weaning, male and female offspring remained on their respective vitamin D level or were switched and fed a high fat and sucrose diet until killing (age 7 months). Bacteroides and Prevotella were quantified in dams' feces and offspring colonic contents. LPS concentrations, bone mineral density and content, strength and structure data were integrated from our previous studies in the same mice. Spearman correlations were completed between Bacteroides and LPS, and bone outcomes. RESULTS: There was a maternal vitamin D effect on colonic Bacteroides but not Prevotella (dam diet: <0.001 and 0.735) in adult male offspring, independent of dams fecal Bacteroides before birth (P=0.998). In males, but not females, Bacteroides correlated with LPS (r=-0.488, P=0.018), trabecular femur peak load (r=0.362, P=0.033), vertebral trabecular separation (r=-0.605, P=0.006), trabecular number (r=0.614, P=0.005) and bone volume fraction (r=0.549, P=0.015). CONCLUSIONS: Dietary vitamin D programs Bacteroides in male adult offspring only, which correlated negatively with systemic inflammation and positively with bone strength and structure. This may have implications on maternal diet and nutritional guidelines targeting sexes in a different manner.

Investigation of cerebral venous outflow in microgravity.

OBJECTIVE: The gravitational gradient is the major component to face when considering the physiology of venous return, and there is a growing interest in understanding the mechanisms ensuring the heart filling, in the absence of gravity, for astronauts who perform long-term space missions. APPROACH: The purpose of the Drain Brain project was to monitor the cerebral venous outflow of a crew member during an experiment on the International Space Station (ISS), so as to study the compensatory mechanisms that facilitate this essential physiological action in subjects living in a microgravity environment. Such venous function has been characterized by means of a novel application of strain-gauge plethysmography which uses a capacitive sensor. MAIN RESULTS: In this contribution, preliminary results of our investigation have been presented. In particular, comparison of plethysmography data confirmed that long duration spaceflights lead to a redistribution of venous blood volume, and showed interesting differences in the amplitude of cardiac oscillations measured at the level of the neck veins. SIGNIFICANCE: The success of the experiment has also demonstrated that thanks to its easy portability, non-invasiveness, and non-operator dependence, the proposed device can be considered as a novel tool for use aboard the ISS. Further trials are now under way to complete the investigation on the drainage function of the neck veins in microgravity.

[Transcient ischemic attack, a rare manifestation of Eagle syndrome]. / Accident ischémique transitoire, une manifestation rare du syndrome d'Eagle.

INTRODUCTION: Clinical presentation of Eagle syndrome (ES) is very variable and non-specific, making its diagnosis difficult. It is usually limited to pain. Transient neurological manifestations are exceptional. We report one case in which the diagnosis of ES has been made based on neurological events occurring during left anterolateral head bending, without pain. OBSERVATION: A 47-year-old man presented with transient neurological events progressing since two years, half-right body paresthesia and reduced field of vision on the left side type, triggered by left anterolateral head flexion and regressive in neutral position. Transcranial Doppler and CT angiography of the supra-aortic trunks were performed in neutral position and in right and left head rotation that showed a disruption of the left sylvian flow and an extrinsic compression of the left internal carotid artery, due to a musculoskeletal impediment involving the lower end of the temporal styloid process. Complete recovering was achieved after surgical resection of this process. A control CT angiography confirmed the cessation of the compression. DISCUSSION: ES has non-specific and highly variable clinical manifestations making diagnosis difficult or leading to misdiagnosis. ES should be considered in any transient neurological deficit, especially when occurring during head rotation. Treatment relies on surgical resection of the excessively long styloid process.

Maternal vitamin D beneficially programs metabolic, gut and bone health of mouse male offspring in an obesogenic environment.

BACKGROUND/OBJECTIVES: Vitamin D is an anti-inflammatory nutrient and a determinant of bone health. Some prospective studies suggest that maternal vitamin D status is positively associated with offspring bone mass. We found that serum concentrations of lipopolysaccharide (LPS), an inflammatory molecule related to adiposity, insulin resistance and bone resorption, is lower in healthy mouse offspring exposed to high dietary vitamin D during pregnancy and lactation. LPS reaches the circulation via the gut. This study investigated whether maternal vitamin D programs metabolic, gut and bone health of male offspring in an obesogenic environment. METHODS: C57BL/6J dams received an AIN-93G diet with high (H) or low (L) vitamin D during pregnancy and lactation. At weaning, offspring remained on their dam's vitamin D level (LL or HH) or were switched (LH or HL) and fed a high fat (44.2%) and sucrose (19.8%) diet. Glucose response, adiposity, systemic inflammation (LPS, cytokines), intestinal permeability and mass, strength and microarchitecture of trabecular and cortical bone were assessed in 7-month-old male offsprings. RESULTS: Higher maternal dietary vitamin D resulted in lower intestinal permeability (fecal albumin, P=0.010) and benefited trabecular but not cortical bone structure at the distal femur (higher trabecular number, P=0.022; less trabecular separation, P=0.015) and lumbar vertebra 2 (bone volume/total volume%, P=0.049). Higher maternal and offspring vitamin D resulted in lower fasting glucose (HH versus LL, P=0.039) and serum LPS concentrations (dam diet, P=0.011; pup diet, P=0.002). Higher offspring vitamin D resulted in lower epididymal fat pad relative weight (P=0.006). The serum concentrations of IL-6 and TNF-α did not differ among groups. CONCLUSIONS: Maternal dietary vitamin D beneficially programs intestinal permeability and systemic LPS concentration, which is accompanied by stronger trabecular bone in an obesogenic environment. Thus, the gut may mediate vitamin D effects. Moreover, optimizing vitamin D in early life may be critical for later health.

Validation of a Hemodynamic Model for the Study of the Cerebral Venous Outflow System Using MR Imaging and Echo-Color Doppler Data.

BACKGROUND AND PURPOSE: A comprehensive parameter model was developed to investigate correlations between cerebral hemodynamics and alterations in the extracranial venous circulation due to posture changes and/or extracranial venous obstruction (stenosis). The purpose of this work was to validate the simulation results by using MR imaging and echo-color Doppler experimental blood flow data in humans. MATERIALS AND METHODS: To validate the model outcomes, we used supine average arterial and venous extracerebral blood flow, obtained by using phase-contrast MR imaging from 49 individuals with stenosis in the acquisition plane at the level of the disc between the second and third vertebrae of the left internal jugular vein, 20 with stenosis in the acquisition plane at the level of the disc between the fifth and sixth vertebrae of the right internal jugular vein, and 38 healthy controls without stenosis. Average data from a second group of 10 healthy volunteers screened with an echo-color Doppler technique were used to evaluate flow variations due to posture change. RESULTS: There was excellent agreement between experimental and simulated supine flows. Every simulated CBF fell inside the standard error from the corresponding average experimental value, as well as most of the simulated extracerebral arterial flow (extracranial blood flow from the head and face, measured at the level of the disc between second and third vertebrae) and venous flows. Simulations of average jugular and vertebral blood flow variations due to a change of posture from supine to upright also matched the experimental data. CONCLUSIONS: The good agreement between simulated and experimental results means that the model can correctly reproduce the main factors affecting the extracranial circulation and could be used to study other types of stenotic conditions not represented by the experimental data.

A simulation model to study the role of the extracranial venous drainage pathways in intracranial hemodynamics.

Alterations in the extracranial venous circulation due to posture changes, and/or extracranial venous obstructions in patients with vascular diseases, can have important implications on cerebral hemodynamics. A hemodynamic model for the study of cerebral venous outflow was developed to investigate the correlations between extracranial blood redistributions and changes in the intracranial environment. Flow data obtained with both magnetic resonance (MR) and Echo-Color Doppler (ECD) technique are used to validate the model. The very good agreement between simulated supine and upright flows and experimental results means that the model can correctly reproduce the main factors affecting the extracranial venous circulation.

A new hemodynamic model for the study of cerebral venous outflow.

We developed a mathematical model of the cerebral venous outflow for the simulation of the average blood flows and pressures in the main drainage vessels of the brain. The main features of the model are that it includes a validated model for the simulation of the intracranial circulation and it accounts for the dependence of the hydraulic properties of the jugular veins with respect to the gravity field, which makes it an useful tool for the study of the correlations between extracranial blood redistributions and changes in the intracranial environment. The model is able to simulate the average pressures and flows in different points of the jugular ducts, taking into account the amount of blood coming from the anastomotic connections; simulate how the blood redistribution due to change of posture affects flows and pressures in specific points of the system; and simulate redistributions due to stenotic patterns. Sensitivity analysis to check the robustness of the model was performed. The model reproduces average physiologic behavior of the jugular, vertebral, and cerebral ducts in terms of pressures and flows. In fact, jugular flow drops from ∼11.7 to ∼1.4 ml/s in the passage from supine to standing. At the same time, vertebral flow increases from 0.8 to 3.4 ml/s, while cerebral blood flow, venous sinuses pressure, and intracranial pressure are constant around the average value of 12.5 ml/s, 6 mmHg, and 10 mmHg, respectively. All these values are in agreement with literature data.